Respiratory epithelium

About: Respiratory epithelium is a research topic. Over the lifetime, 5048 publications have been published within this topic receiving 222304 citations. The topic is also known as: respiratory tract epithelium & Respiratory Mucosa.

Selective infections of olfactory and respiratory epithelium by vesicular stomatitis and sendai viruses

Abstract: Following intranasal instillation of vesicular stomatitis virus (VSV) in mice there was an extensive infection of the olfactory epithelium in contrast to a minimal involvement of the respiratory epithelium Sendai virus (SV), on the other hand, caused an extensive infection of the respiratory epithelium and only minimal infection of the olfactory mucous membrane VSV budded from basolateral surfaces of supporting cells and olfactory neurons, but not from their apical surfaces or the ciliated bulbous endings of the olfactory neuron dendrites This asymmetric release of VSV favoured neuroinvasion The virus spread along the olfactory nerves to the glomeruli in the olfactory bulbs after which it propagated transneuronally into the rest of the brain SV budded only from the apical surface of respiratory epithelial cells, was released into the air passages, and there were no signs of invasion into the olfactory bulbs Inoculation of the olfactory mucous membrane is a useful procedure for studies on selectivity of attack on peripheral neurons by viruses and on mechanisms of virus invasion of the nervous system in vivo

Oxidative stress serves as a key checkpoint for IL-33 release by airway epithelium.

Abstract: Background Interleukin (IL)-33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL-33 release is controlled. The transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a key role in antioxidant response regulation. Objective The goal of this project was to investigate the role of cellular oxidative stress in controlling IL-33 release in airway epithelium. Methods Complementary approaches were used that included human bronchial epithelial cells and mouse models of airway type-2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me) was used to evaluate the role of Nrf2-induced antioxidant molecules. Results Human bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N-acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL-33 release. Administration of CDDO-Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO-Me treatment reduced allergen-induced ATP secretion and IL-33 release by airway epithelial cells in vitro and protected mice from IL-33 release and asthma-like pathological changes in the lungs. Conclusions The balance between oxidative stress and antioxidant responses plays a key role in controlling IL-33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.

Pseudomonas stimulates interleukin-8 mRNA expression selectively in airway epithelium, in gland ducts, and in recruited neutrophils.

Abstract: Neutrophils may play important roles in chronic airway diseases. Pseudomonas is a common pathogen in some chronic airway diseases, and expression of the neutrophil chemoattractant interleukin-8 (IL-8) is induced by Pseudomonas in various cells in vitro. Here we examine the localization of IL-8 mRNA expression after incubating human and dog bronchi with Pseudomonas supernatant in vitro. To examine IL-8 expression in recruited neutrophils, we also superfused the dog bypassed tracheal segment with Pseudomonas supernatant in vivo and measured neutrophil number and IL-8 concentration in luminal fluid; simultaneously, we introduced Pseudomonas supernatant by catheter in a peripheral airway. After 6 h, we analyzed IL-8 mRNA expression and localization in removed tissue. Unincubated bronchi showed no IL-8 mRNA expression, but incubation with Pseudomonas supernatant in vitro resulted in IL-8 mRNA expression in surface epithelial, gland duct, and a subpopulation of serous gland cells. In vivo, introduction of Pseudomonas supernatant into dog trachea and peripheral airways caused IL-8 mRNA expression in epithelial and gland duct cells but also in the recruited neutrophils. Pseudomonas lipopolysaccharide alone was without effect in vitro and in vivo. We conclude that Pseudomonas products, but not lipopolysaccharide, stimulate IL-8 expression in airways and that this expression occurs primarily in surface epithelial and gland duct cells, thus bringing the chemoattractant to the bacterial site. Furthermore, IL-8 expression in recruited neutrophils provides a potential mechanism for positive feedback of this protective antibacterial response.

Dysfunctional cystic fibrosis transmembrane conductance regulator inhibits phagocytosis of apoptotic cells with proinflammatory consequences.

Abstract: Cystic fibrosis (CF) is caused by mutated CF transmembrane conductance regulator (CFTR) and is characterized by robust airway inflammation and accumulation of apoptotic cells. Phagocytosis of apoptotic cells (efferocytosis) is a pivotal regulator of inflammation, because it prevents postapoptotic necrosis and actively suppresses release of a variety of proinflammatory mediators, including IL-8. Because CF is associated with accumulation of apoptotic cells, inappropriate levels of IL-8, and robust inflammation, we sought to determine whether CFTR deficiency specifically impairs efferocytosis and its regulation of inflammatory mediator release. Here we show that CFTR deficiency directly interferes with efferocytosis by airway epithelium, an effect that is not due to altered binding of apoptotic cells to epithelial cells or altered expression of efferocytosis receptors. In contrast, expression of RhoA, a known negative regulator of efferocytosis, is substantially increased in CFTR-deficient cells, and inhibitors of RhoA or its downstream effector Rho kinase normalize efferocytosis in these cells. Impaired efferocytosis appears to be mediated through an amiloride-sensitive ion channel, because amiloride restores phagocytic competency in CFTR-deficient cells. Finally, ineffective efferocytosis in CFTR-deficient cells appears to have proinflammatory consequences, because apoptotic cells enhance IL-8 release by these cells, but not by wild-type controls. Therefore, in CF, dysregulated efferocytosis may lead to accumulation of apoptotic cells and impaired regulation of the inflammatory response and, ultimately, may suggest a new therapeutic target.

The role of respiratory epithelium in a rat model of obliterative airway disease.

Abstract: Fibrotic obliteration of the terminal airways is the majorlong-term complication after lung transplantation. The dis-ease obliterative bronchiolitis (OB*) is nondiscriminatory interms of single-lung, double-lung, or heart-lung transplanta-tion and has been observed with prevalence of 50% by 5 yearsafter transplantation. Pathologically, OB begins with inflam-mation of the terminal airways, including a lymphocytic in-filtration of the bronchiolar walls and mucosa. Damagednative epithelium becomes necrotic and often sloughs intothe airway. Mesenchymal cells in the submucosa proliferate,and eventually collagen-rich granulation tissue progressivelyinvades and occludes the bronchial lumen (